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Depression: 21st Century Solutions + The Dark Side of Wheat

Abstract Title:

Curcumin promotes apoptosis, increases chemosensitivity, and inhibits nuclear factor kappaB in esophageal adenocarcinoma.

Abstract Source:

Transl Oncol. 2010 Apr;3(2):99-108. PMID: 20360934

Abstract Author(s):

Wibisono Hartojo, Amy L Silvers, Dafydd G Thomas, Christopher W Seder, Lin Lin, Hyma Rao, Zhuwen Wang, Joel K Greenson, Thomas J Giordano, Mark B Orringer, Alnawaz Rehemtulla, Mahaveer S Bhojani, David G Beer, Andrew C Chang

Article Affiliation:

Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.

Abstract:

The transcription factor, nuclear factor kappaB (NF-kappaB), plays a central role as a key mediator of cell survival and proliferation, and its activation may confer increased tumor chemoresistance. Curcumin, an orally available naturally occurring compound, has been shown to inhibit NF-kappaB and has a potential role in cancer chemoprevention. We investigated the effects of curcumin on NF-kappaB activity, on cell viability, and as a chemosensitizing agent with 5-fluorouracil (5-FU) or cisplatin (CDDP) in esophageal adenocarcinoma (EAC). Oligonucleotide microarray analysis of 46 cases, consisting of Barrett metaplasia, low-grade dysplasia, high-grade dysplasia and EAC, showed increased expression of NF-kappaB and IkappaB kinase subunits and decreased effector caspase expression in EAC compared with Barrett metaplasia. Stromal expression of both IkappaB and phospho-IkappaB was detected in several EAC samples by tissue microarray analysis. Curcumin alone inhibited NF-kappaB activity and induced apoptosis in both Flo-1 and OE33 EAC cell lines as determined by Western blot analysis, NF-kappaB reporter assays, and Caspase-Glo 3/7 assays. It also increased 5-FU- and CDDP-induced apoptosis in both cell lines. These data suggest that activation of NF-kappaB and inhibition of apoptosis may play a role in the progression from Barrett metaplasia to EAC. In addition, curcumin, a well-known inhibitor of NF-kappaB activity, was shown to increase apoptosis and enhance both 5-FU- and CDDP-mediated chemosensitivity, suggesting that it may have potential application in the therapy of patients with EAC.

Study Type : In Vitro Study

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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